Transcriptional enhanced associate domain (TEAD) transcription factors play important roles during development, cell proliferation, regeneration, and tissue homeostasis. TEAD integrates with and coordinates various signal transduction pathways including Hippo, Wnt, transforming growth factor beta (TGFβ), and epidermal growth factor receptor (EGFR) pathways. TEAD deregulation affects well-established cancer genes such as KRAS, BRAF, LKB1, NF2, and MYC, and its transcriptional output plays an important role in tumor progression, metastasis, cancer metabolism, immunity, and drug resistance. To date, TEADs have been recognized to be key transcription factors of the Hippo pathway. Therefore, most studies are focused on the Hippo kinases and YAP/TAZ, whereas the Hippo-dependent and Hippo-independent regulators and regulations governing TEAD only emerged recently. Deregulation of the TEAD transcriptional output plays important roles in tumor progression and serves as a prognostic biomarker due to high correlation with clinicopathological parameters in human malignancies. In addition, discovering the molecular mechanisms of TEAD, such as post-translational modifications and nucleocytoplasmic shuttling, represents an important means of modulating TEAD transcriptional activity. Collectively, this review highlights the role of TEAD in multistep-tumorigenesis by interacting with upstream oncogenic signaling pathways and controlling downstream target genes, which provides unprecedented insight and rationale into developing TEAD-targeted anticancer therapeutics.

Nowadays, the exploration of zinc oxide nanoparticles (ZnO NPs) based products is booming in the various directions of bio-nanomedicine and other consumer products, but the comprehensive toxicological impact posed by ZnO NPs still remains unclear. The present study systematically investigates and correlates the toxicity evaluation of ZnO NPs in RAW 264.7 murine macrophages (in vitro) and male ICR mice (in vivo) by two different administration routes, i.e. g.i. and i.p. at different doses. The in vitro studies showed a slight rise in intracellular reactive oxygen species level (ROS), NF-κB transcription factor expression (TF) and NPs uptake at higher dose, indicating the non-toxic nature of ZnO NPs below 100 μg mL⁻¹ doses. The in vivo results demonstrate a slight gain in body weight (BW), reduction in the organ weight, mild to severe pathological alteration in the organs depending upon NP dosage and mode of administration routes. The histopathological investigation suggests that the liver, kidney, lung, spleen, and pancreas may be the target organs for ZnO NPs according to the administration routes. Serum biochemistry assay shows an elevation in the GPT and ALP level, suggesting liver dysfunction. To our knowledge, this is the first study to report the toxic effects of ZnO NPs through i.p. administration. Further, the present work will offer a deeper understanding regarding the toxicology and in vivo behaviours of ZnO NPs in mice depending upon the various administration routes.

Endoplasmic reticulum (ER) stress is associated with the pathogenesis of hepatic steatosis. Alisma orientale Juzepzuk is a traditional medicinal herb for diuretics, diabetes, hepatitis, and inflammation. In this study, we investigated the protective effects of methanol extract of the tuber of Alisma orientale (MEAO) against ER stress-induced hepatic steatosis in vitro and in vivo. MEAO inhibited the tunicamycin-induced increase in luciferase activity of ER stress-reporter constructs containing ER stress response element and ATF6 response element. MEAO significantly inhibited tunicamycin-induced ER stress marker expression including GRP78, CHOP, and XBP-1 in tunicamycin-treated Human hepatocellular carcinoma (HepG2) cells and the livers of tunicamycin-injected mice. It also inhibited tunicamycin-induced accumulation of cellular triglyceride. Similar observations were made under physiological ER stress conditions such as in palmitate (PA)-treated HepG2 cells and the livers of high-fat diet (HFD)-induced obese mice. MEAO repressed hepatic lipogenic gene expression in PA-treated HepG2 cells and the livers of HFD obese mice. Furthermore, MEAO repressed very low-density lipoprotein receptor (VLDLR) expression and improved ApoB secretion in the livers of tunicamycin-injected mice or HFD obese mice as well as in tunicamycin or PA-treated HepG2 cells. Alismol, a guaiane-type sesquiterpenes in Alisma orientale, inhibited GRP78 expression in tunicamycin-treated HepG2 cells. In conclusion, MEAO attenuates ER stress and prevents hepatic steatosis pathogenesis via inhibition of expression of the hepatic lipogenic genes and VLDLR, and enhancement of ApoB secretion.